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Published on: February 15, 2015
NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance
1Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut, USA.
Summary
NMDA receptor antagonists impair prefrontal cortex cognitive functions in rats. Dopamine release in the prefrontal cortex contributes to this impairment, suggesting a link between glutamate and dopamine in cognition.
Area of Science:
- Neuroscience
- Cognitive Science
- Pharmacology
Background:
- The prefrontal cortex (PFC) is crucial for associative cognitive functions.
- Excitatory amino acid and dopamine receptors play significant roles in PFC function.
Purpose of the Study:
- To investigate the role of NMDA (N-methyl-D-aspartate) receptors and dopamine receptors in PFC-dependent associative functions.
- To examine the effects of NMDA antagonists and dopamine antagonists on cognitive tasks and dopamine release in the rat PFC.
Main Methods:
- Spatial delayed alternation task to assess PFC-sensitive cognitive performance.
- In vivo microdialysis to measure dopamine release in the rat PFC.
- Administration of ketamine, MK-801 (NMDA antagonists), raclopride, SCH-23390, and haloperidol (dopamine antagonists).
Main Results:
- Ketamine and MK-801 dose-dependently impaired spatial delayed alternation performance.
- Dopamine antagonists alone did not significantly affect performance.
- Haloperidol and raclopride reversed ketamine-induced cognitive deficits.
- Ketamine increased dopamine release in the PFC.
Conclusions:
- Glutamatergic neurotransmission via NMDA receptors is essential for PFC-dependent cognitive functions.
- Dopamine neurotransmission contributes to the cognitive impairments induced by NMDA receptor blockade in the PFC.
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